1. Field of the Invention
The present invention is directed to pharmaceutical compositions, and primarily to topically applied ophthalmic compositions comprising as the active ingredient one or more gamma amino butyric acid agonist compounds. The pharmaceutical compositions are useful for reducing intraocular pressure in animals of the mammalian species. In another aspect, the present invention is directed to administering such formulations and compositions to animals of the mammalian species (including humans) for reducing intraocular pressure in the eye.
2. Brief Description of the Prior Art
Glaucoma is an optical neuropathy associated with elevated intraocular pressures which are too high for normal function of the eye, and results in irreversible loss of visual function. It is estimated in medical science that glaucoma afflicts approximately 2 per cent of the population over the age of forty years, and is therefore a serious health problem. Ocular hypertension, i.e. the condition of elevated intraocular pressure, which has not yet caused irreversible damage, is believed to represent the earliest phase of glaucoma. Many therapeutic agents have been devised and discovered in the prior art for the treatment or amelioration of glaucoma and of the condition of increased intraocular pressure which precedes glaucoma.
Gamma amino butyric acid (H.sub.2 N(CH.sub.2).sub.3 COOH, GABA) is a natural metabolite, a break-down product of glutamine and a major inhibitory neurotransmitter. Its chemical structure can be described as an aliphatic carboxylic acid which carries an amino function on the terminal carbon of the aliphatic chain.
The concept of gamma amino butyric acid (GABA) receptors has been known in the biological sciences for a long time. According to the classical definition, GABA receptors of living organisms, (including mammals and particularly humans) are those biological receptor sites which are activated by GABA. Agonist of a receptor are those compounds or substances which bind to the receptor site and elicit a response. Accordingly, agonist of GABA receptors are those compounds which bind to and elicit a response on GABA receptor sites. The compound gamma aminobutyric acid itself by definition, is a GABA agonist, and several other GABA agonist are known in the pharmaceutical and related sciences.
The following patents (and other references) are believed to be pertinent as background to the present invention, either because they describe or relate to compounds or compositions for reducing intraocular pressure (anti-glaucoma), or because they relate to the biological activity of GABA or structurally related compounds.
U.S. Pat. No. 3,644,643 describes a process of systemically administering glycine (an amino acid) for the purpose of reducing intraocular pressure.
U.S. Pat. No. 4,837,021 describes an irrigating solution for irrigating exposed eye tissue during surgery for the purpose of preventing or ameliorating injury to the exposed eye tissue, which solution includes GABA or a functional equivalent analog.
U.S. Pat. No. 4,171,377 discloses an ophthalmic solution which is applied topically to injured or swollen cornea to reduce swelling and promote epithelial healing, which solution contains trans-4-(aminomethyl) cyclohexanecarboxylic acid (tranexamic acid) as the active ingredient.
U.S. Pat. No. 4,363,818 discloses a method for drying and diminution of cutaneous and mucosal lesions by topically applying a solution which contains as the active ingredient .epsilon.-aminocaproic acid (NH.sub.2 -(CH.sub.2).sub.5 COOH) or other isomers of aminocaproic acid.
U.S. Pat. No. 4,322,440 refers to still earlier literature references regarding systemic administration of GABA agonists, and that such administration does not provide a useful anti-convulsant effect. The patent nevertheless describes amino carboxylic acids (and simple derivatives) where the carboxylic function and the amino function are separated by 3 or 4 methylene (CH.sub.2) units, and which have anti-convulsant and anxiolytic activities.
Additional examples of background art to the present invention directed to intraocular hypotensive and anti-glaucoma agents can be found in the following U.S. Pat. Nos. 3,467,756; 4,197,301; 4,565,821; 5,066,664 and 5,091,528.
The foregoing and other anti-glaucoma and ocular hypotensive compounds and agents of the prior art do not provide such treatment or cure for glaucoma and ocular hypertension which is satisfactory in all respects. Therefore, the pharmacological and related arts continue searching for additional and better anti-glaucoma and ocular hypotensive agents. The present invention represents a significant advance step in this direction.